The synthesis of three sets of 7-substituted-4-hydroxyquinoline-3-carboxylic acids as inhibitors of malic acid dehydrogenase is proposed. Substituent variations within each set have been selected from published cluster analysis to insure a maximum range and minimum covariance in the hydrophobic, electronic, and polar properties of the congeners. Inhibition of malic acid dehydrogenase and lactic acid dehydrogenase will be measured, and a comparative, quantitative correlation analysis conducted to further characterize the physicochemical binding environment at the enzyme active sites. These initial correlations will be utilized in the design of an extended set of inhibitors in order to maximize selective inhibition of malic acid dehydrogenase as a means of developing potential antineoplastic agents that inhibit cellular respiration.